a new view of the bacterial cytosol environment一个新的视图细菌细胞溶质的环境.pdfVIP

A New View of the Bacterial Cytosol Environment 1 2 1 Benjamin P. Cossins , Matthew P. Jacobson , Victor Guallar * 1 Department of Life Science, Barcelona Supercomputer Center, Barcelona, Spain, 2 Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America Abstract The cytosol is the major environment in all bacterial cells. The true physical and dynamical nature of the cytosol solution is not fully understood and here a modeling approach is applied. Using recent and detailed data on metabolite concentrations, we have created a molecular mechanical model of the prokaryotic cytosol environment of Escherichia coli, containing proteins, metabolites and monatomic ions. We use 200 ns molecular dynamics simulations to compute diffusion rates, the extent of contact between molecules and dielectric constants. Large metabolites spend ,80% of their time in contact with other molecules while small metabolites vary with some only spending 20% of time in contact. Large non- covalently interacting metabolite structures mediated by hydrogen-bonds, ionic and p stacking interactions are common and often associate with proteins. Mg2+ ions were prominent in NIMS and almost absent free in solution. K+ is generally not involved in NIMSs and populates the solvent fairly uniformly, hence its important role as an osmolyte. In simulations containing ubiquitin, to represent a protein component, metabolite diffusion was reduced owing to long lasting protein- metabolite interactions. Hence, it is likely that with larger proteins metabolites would diffuse even more slowly. The dielectric constant of these simulations was found to differ from that of pure water only throu